Role of the blood coagulation cascade in hepatic fibrosis

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 315; no. 2; pp. G171 - G176
• Main Authors: Pant, Asmita, Kopec, Anna K., Luyendyk, James P.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2018
• Series: Liver and Biliary Tract Physiology/Pathophysiology
• Subjects: Animals; Blood coagulation; Blood Coagulation - physiology; Blood Coagulation Factors - metabolism; Cirrhosis; Clotting; Coagulation; Coagulation factor Xa; Fibrosis; Hemorrhage; Humans; Liver cirrhosis; Liver Cirrhosis - blood; Liver diseases; Mini-Review; Risk factors; Thrombin; Thrombosis; anticoagulants; fibrosis; liver; coagulation
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00402.2017

Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis. Indeed, strong evidence drawn from experimental animal studies indicates that components of the coagulation cascade, particularly coagulation factor Xa and thrombin, drive profibrogenic events, leading to hepatic fibrosis. Here, we concisely review the evidence supporting a pathologic role for coagulation in the development of liver fibrosis and the potential mechanisms involved. Further, we highlight how studies in experimental animals may shed light on emerging clinical evidence, suggesting that beneficial effects of anticoagulation could extend beyond preventing thrombotic complications to include reducing pathologies like fibrosis.